OBJECTIVES:
To estimate the predictive value of diurnal voiding symptoms for the diagnosis
of bladder dysfunction in enuretic children and teenagers receiving care at
Fernandes Figueira Institute (Rio de Janeiro, Brazil). METHODS: From June 1999 to May 2002, 91 patients (aged 5-17 years) with
enuresis, both monosymptomatic and polysymptomatic, were assessed based on medical
history, voiding chart, physical examination, and urodynamic studies. The medical
history was investigated for detection of diurnal voiding symptoms. The predictive
value of these symptoms for the diagnosis of bladder dysfunction was estimated.
RESULTS: Bladder dysfunction was observed in 94.5% of the children and
teenagers with enuresis. Medical history identified 97.3% of patients with diurnal
voiding symptoms. Increased discharge of urine was detected exclusively by voiding
chart in only 2.7% of the patients. The positive predictive value of diurnal
voiding symptoms for bladder dysfunction was 98.6%. There was a statistically
significant association between diurnal voiding symptoms and bladder dysfunction
(p < 0.005). The risk for bladder dysfunction was approximately 20 times
higher in presence of these symptoms. CONCLUSIONS: The presence of diurnal voiding symptoms was a strong predictor
of bladder dysfunction. Medical history was a useful instrument for detecting
diurnal voiding symptoms and establishing the diagnosis of bladder dysfunction.

Enuresis, urinary
incontinence, bladder dysfunction.

Introduction

The most often
employed definition of enuresis is "involuntary urination at an age at
which control should already have been achieved".1,2 It is classified
as nocturnal when involuntary urination occurs during sleep and diurnal when
the child is awake.2-5 The American Psychiatric Association 's
definition of enuretic covers children who are still wetting at five years or
more.2

The International
Children's Continence Society (ICCS)6 defines enuresis as normal
urination occurring at times or in places that are socially unacceptable.

Some children
with nocturnal enuresis are quite able to control urination during the daytime.
The term monosymptomatic nocturnal enuresis has come to be employed to describe
children with urinary behavior that is totally normal during the daytime, or
when awake. Other patients also present diurnal urinary symptoms, such as: increased
frequency of urination, incontinence, urge incontinence, maneuvers to prevent
urine escape, an interrupted urinary flow and hesitation when starting to urinate.
Such patients are classified as suffering from polysymptomatic enuresis . It
is important that such clinical manifestations be investigated, even when there
is no evidence or urinary incontinence, because of the possibility of voiding
dysfunction.3,6-9

Voiding dysfunction
occurs when one of the elements of the normal voiding process is affected, causing
it to no longer function correctly. Thus abnormalities in the cortex, the brainstem,
the spinal marrow, the detrusor or the sphincter complex may result in unsatisfactory
urination, with inadequate urine storage and/or incomplete emptying of the bladder.10

Functional abnormalities
of the lower urinary tract can be split into two groups: those that are caused
by neurological abnormalities and those that are functional.

Voiding abnormalities
caused by neurological alterations (neurogenic bladder) are most commonly the
result of spinal dysraphisms (myelomeningocele, lipomeningocele, sacral agenesis
and occult lesions) or cerebral palsy.10,11

Urinary dysfunction
resulting from functional abnormalities occur with children in whom evidence
of neurological disease is not found. They may present with the diurnal voiding
dysfunctions listed above or with nocturnal dysfunctions, repeat urinary infections
and vesicoureteral reflux. They often have intestinal constipation in association
and soiling due to dysfunction of the pelvic floor also occurs frequently, in
which case it is described as dysfunctional elimination syndrome.4,12,13
An early diagnosis is important in order that treatment may be initiated which,
in addition to reducing the social and psychological repercussions of incontinence
may avert kidney damage with renal scarring and loss of function..

Nevertheless,
despite their clinical importance, daytime symptoms suggestive of voiding dysfunction
are not always evident and a trained eye is required to detect them. Parents
will often fail to describe daytime symptoms, either because they do not know
about them or because they consider them normal. Other parents may attribute
urge incontinence to laziness on the part of the child who plays until the last
moment instead of going straight to the bathroom as soon as an urge is felt
or who does not go to the toilet before leaving home and so always needs to
stop en route in order to avoid leakage. Usually it is the nocturnal voiding
that motivates them to seek medical advice along with all the disturbance it
causes: pajamas, bedclothes and mattress all wet; parents' sleep interrupted;
the child socially isolated by the embarrassment involved and suffering from
low self-esteem; siblings' lives affected; among many others. Thus, technically
well-founded, detailed anamnesis is of fundamental importance to the evaluation
and classification of these patients.

Urodynamics analysis
enables the confirmation of a lower urinary tract dysfunction diagnosis. Analyses
can be performed of bladder storage and emptying functions and also of urethra
sphincter activity. Pressure can be recorded during filling and emptying of
the bladder (cystometry) and urinary flow can be monitored (uroflowmetry) as
can external urethral sphincter function (electromyography). For enuretic patients
Urodynamics analysis is indicated in the following circumstances: if neurological
abnormalities are suspected, when there are diurnal urination abnormalities
with no obvious primary pathology, with adolescents presenting nocturnal enuresis
resistant to therapy, when there is soiling associated, if voiding difficulties
appear after treatment for urinary infection, in cases of recurrent urinary
infection despite the use of chemoprophylaxis, where there is bladder trabeculation
or a coiled urethra visible with voiding cystourethrography.1,9-11

Urodynamics analysis,
however, is not always available. Furthermore it is considered an invasive examination
due to the need for urethral catheterization. If it were possible to ascertain
whether data obtained from clinical examinations of enuretic patients is capable
of indicating the presence of bladder dysfunction a useful contribution would
be made towards early diagnosis and treatment.

This study was
performed with the following objective:

- Estimate the
predictive power of diurnal symptoms for a diagnosis of voiding dysfunction
in enuretic children and adolescents treated at the Urodynamics Clinic at the
Instituto Fernandes Figueira.

Methods

This was a cross-sectional
study of 91 patients of both sexes aged between 5 and 17 years, suffering either
from monosymptomatic nocturnal enuresis or from nocturnal enuresis associated
with diurnal voiding dysfunction, referred to the Pediatric Urodynamics Clinic
at the Instituto Fernandes Figueira  Fundação Oswaldo Cruz
during the period between June 1999 and May 2002. An enuresis frequency equal
to or greater than once a week was used as an inclusion criterion for the study.

As this is an
cross-sectional study involving dichotomous variables, the rules described by
Browner et al. were used to calculate the n value required for an a
error of 0.05 and a b of 0.10. This calculation returned a minimum n value
of 23 patients.14

- those who
were on anticholinergics, imipramine, DDAVP or other drugs that act on the
detrusor or urethral sphincter at the time of their first consultation.

After approval
had been obtained for the project from the Committee for Ethics in Research
at the Instituto Fernandes Figueira (CERIFF), specialists and pediatricians
working at primary and secondary health centers were informed of its existence
in the hope of widening the sample base. This enabled enuretic patients to be
referred irrespective of their clinical characteristics (mono/multisymptomatic)
and of any clinical suspicion of lower urinary tract dysfunction. As the research
progressed children and adolescents began to arrive having been recommended
by patients at the Urodynamics Clinic. Once their parents had given their consent
the research protocol was applied to these patients too.

The first consultation
consisted of anamnesis and a physical examination; laboratory tests and voiding
maps were requested.

The voiding maps
recorded all nocturnal enuresis episodes for two weeks and all urination and
diurnal voiding during the weekend.

All anamnesis
was performed by the researcher herself. A model was developed (Figure
1) including objective questions about each diurnal urinary symptom. Also
included were: reason for referral, number of enuresis episodes while asleep,
per week and per night, bowel function in terms of constipation and/or soiling,
history of urinary tract infection, the history of the pregnancy, delivery and
neonatal period, neuropsychomotor development history, family history.

The urination frequency
that was considered normal was between 4 and 8 times a day.15-17
This was assessed using the voiding map records and during anamnesis by asking
how many times the child had been to the bathroom while waiting for their consultation
and/or since they got up. In this way, the possibility that the answer depended
entirely on the, often subjective, assessment of the parent or guardian was
avoided.

During the physical
examination emphasis was given to the search for neurocutaneous stigmata in
the lumbar region, to neurological or orthopedic abnormalities and to the examination
of external genitalia.

Urodynamics assessment
was performed with the children cooperating; with no sedation or containment.
Equipment by Dantec was used, either the Duet or Dynamed model, belonging to
the Pediatric Urodynamics Laboratory at the Instituto Fernandes Figueira. Bladders
were filled with saline solution at 0.9% at room temperature (on average 25
to 30 ºC), infused at a rate of 10% of the minimum estimated bladder capacity
for age per minute.6,18

All results were
classified by the same examiner according to International Children's Continence
Society.6

According to this
classification system, Urodynamics findings are considered normal when the bladder
can be filled at low pressures and there is increased internal bladder pressure
during the voiding phase followed by relaxation of the urethral sphincter complex
triggering urination and complete emptying of the bladder. During the fill phase
there should be no involuntary contractions or detrusor inhibition.

In order to estimate
the probability that the patients' enuresis were due to bladder dysfunction
based on diurnal urinary symptoms, positive and negative predictive powers were
calculated.

Associations were
evaluated between voiding dysfunction as diagnosed by Urodynamics assessment
and the following variables: frequency of enuresis episodes, diurnal voiding
behavior abnormalities, primary or secondary enuresis onset, family history
of enuresis, previous history of urinary infection, bowel dysfunction.

Fisher's exact
test was used in order to ascertain whether these associations were statistically
significant. This choice was based on the fact that the expected frequency was
less than 5, which violates one of the conditions for c2
applicability.19 The significance level adopted for a
(alpha) was 0.05. Additionally, the relative risk (odds ratio) of a patient
presenting voiding dysfunction in conjunction with each of these factors.20,21

Results

One hundred and
two patients referred to the IFF Urodynamics Clinic between June 1999 and May
2002 for enuresis were included in the study. Ninety-one of these patients completed
the diagnostic protocol. Among those who did not complete the process were three
children who refused the urodynamic examination.

Patient age varied
from 5 to 17 years. Forty-five (49.5%) patients were female and 46 (50.5%) were
male (p > 0.882).

Patient distribution
according to number of enuresis episodes per week can be observed in Table
1. The fact that 93.4% presented three or more episodes per week stands
out.

Initial attendance
was motivated by nocturnal enuresis in 57 (62.6%) cases and nocturnal enuresis
associated with diurnal signs and symptoms in 34 (37.4%). After directed anamnesis
and the completion of a voiding map, these patients were reclassified by enuresis
type. Anamnesis identified diurnal symptoms in 71 (97.3%) patients allowing
for correct diagnosis of enuresis type. In just two (2.7%) patients, elevated
urination frequency was observed by means of the voiding map, but not detected
by anamnesis.

As can be seen
in the graph in Figure 2, after reclassification the number
of monosymptomatic nocturnal enuresis suffers (MNE) fell from 57 (62.6%) to
18 (31.6%) and the number of polysymptomatic sufferers increased from 34 (37.4%)
to 73 (68.4%) (p < 0.001). Even excluding patients who were referred by laypeople
(Urodynamics patients and a teacher) and taking into account only those patients
who had been referred by a doctor, the difference between pre and post reclassification
remained statistically significant. Excluding these patients the number of MNE
sufferers dropped from 46 (60.5%) to 15 (19.7%) and the number of polysymptomatic
enuresis sufferers increased from 30 (39.5%) to 61 (80.3%) (p < 0.001).

Urodynamics findings
were compatible with voiding dysfunction in 86 (94.5%) cases. Fourteen (77.8%)
of these were suffering from MNE and 72 (98.6%) of them presented diurnal symptoms
in association with nocturnal enuresis (Table 2). The main
Urodynamics abnormalities found were: reduced bladder capacity in 76 (83.5%)
patients and uninhibited contractions in 62 (68.1%). Four (4.4%) patients presented
post-voiding contraction.

Voiding dysfunction
was more common among patients with higher numbers of nocturnal enuresis episodes
per week (p = 0.005). Patients suffering from two or less episodes of nocturnal
enuresis per week had a lower risk of presenting voiding dysfunction than those
who experienced three or more episodes per week (odds ratio = 0.07; 95% confidence
interval: 0.01 < OR < 0.87; p = 0.033) (Figure 3).

There was an association
between presence/absence of diurnal symptoms, as detected by anamnesis and notes
on the map, and voiding dysfunction as verified by the Fisher test (p < 0.005).
The risk of Urodynamics findings being abnormal was around 20 times greater
among patients who presented diurnal symptoms (odds ratio = 20.27; 95% confidence
interval: 1.87 < OR < 532.00) than for patients suffering from MNE.

The use of anamnesis
together with the voiding map to detect diurnal urination pattern abnormalities
returned a high positive predictive value for a diagnosis of voiding dysfunction.
Thus, the probability that any given patient with diurnal symptoms associated
with nocturnal enuresis would present voiding dysfunction was 98.6%. In contrast,
however, the probability that a patient with MNE would not present voiding dysfunction
(negative predictive value) was just 22.2%. The proportion of patients with
voiding dysfunction who presented diurnal symptoms associated with nocturnal
enuresis (sensitivity) was 83.7%. The proportion of patients with without voiding
dysfunction who presented MNE (specificity) was 80%.

The presence of
diurnal urination symptoms was the primary risk factor for a diagnosis of voiding
dysfunction among the children e adolescents. There was also a statistical association
between voiding dysfunction and the following factors: case history suggestive
of CNS damage and an enuresis frequency greater than three nights per week.
All of these are detectable by anamnesis  an instrument that is inherent
to medical consultations. The results of analysis of the remaining variables
such as: primary or secondary onset, bowel dysfunction, previous history of
urinary infection, a perinatal history at risk of CNS damage and family enuresis
history can be seen in Table 3.

Discussion

Our study revealed
an elevated percentage of voiding dysfunction sufferers among children treated
for enuresis at the Urodynamics Clinic of the Instituto Fernandes Figueira.
This percentage was greater than those found in other studies.22,23

The frequency
of nocturnal wetting exhibited a statistically significant association with
voiding dysfunction. Patients suffering more than three enuresis episodes per
week also presented a higher risk of voiding dysfunction. The high percentage
of patients wetting more than three nights a week may have contributed to the
high dysfunction prevalence found.

The fact that
the Instituto Fernandes Figueira is a center of excellence in the field of pediatric
urodynamics may also cause a selection bias towards patients with a clinical
suspicion of voiding dysfunction. Making the research project public through
basic health centers and deciding to accept patients referred by other patients
were methods for reducing this bias. These two sources were responsible for
the inclusion, of more than half of the study population.

The majority of
the patients (62.7%) were referred by pediatricians, which was largely an expression
of the response to publicizing the research project. This provides evidence
of the importance of making pediatricians aware of the possibility of clinical
recognition of voiding dysfunction among patients suffering from enuresis, since
they are who care for these children in the first instance.

Patients referred
for MNE represented 62.6% of those included in the study. However, after anamnesis
and the voiding map were applied, only 19.8% of the patients remained in this
category. If the group of patients referred by doctors are considered in isolation,
the reduction in MNE sufferers after anamnesis was also significant. Literature
reviews reinforce the impression that, after more detailed analysis, the percentage
of patients with MNE tends to drop. Chandra claims that 48% of boys and 70%
of girls referred to their service due to nocturnal enuresis only, also presented
diurnal symptoms.3 Similarly, an earlier study in which we compared the reason
for the referral of 72 children suffering from enuresis or urinary incontinence
with a diagnosis after directed anamnesis, showed that more than half of the
children referred for nocturnal enuresis also presented diurnal symptoms not
previously noted.24 These findings appear, at least partly, to be
related to the conception of enuresis as exclusively a behavioral problem or
as a family inheritance that will improve over time. Added to this is the average
pediatrician's unfamiliarity with voiding functions and the difficulty of clinical
identification of diurnal urinary dysfunctional symptoms. The MNE proportions
found after reclassification (19.8%) were lower than those described in other
studies. Rawashdeh et al.25 found 74.1%, Yang et al.26
48%, Cigna et al.23 25.7% of MNE. The lack of agreement is probably
due to methodological differences, such as the details of the anamnesis model,
and the bias referred to earlier.

Work which lists
more rigorous methodological criteria for diurnal symptoms in general involves
smaller samples, using less than 20 patients.27,28 Glazener &
Evans performed a systematic analysis of the use of alarms with children with
nocturnal enuresis. Of the 952 potentially relevant primary studies, only 22
were of sufficient quality to be included in the analysis and of these only
four excluded patients with diurnal symptoms.29

Some of the most
important publications on nocturnal enuresis prevalence, such as the classic
by Fergusson et al., were written more than twenty years ago. At that time,
current voiding dysfunction knowledge did not exist and the emphasis on separating
MNE from enuresis associated with other urinary, intestinal or neurological
symptoms.30

These facts provide
evidence of the need for systematic research into diurnal symptoms by means
of directed anamnesis and voiding map. The validity of the anamnesis model employed
has been demonstrated by its ability to identify the existence of voiding abnormalities
in 97.3% of those affected. The importance of this screening process becomes
evident when we consider that the risk of an enuretic patient having voiding
dysfunction is 20 times greater when diurnal symptoms are exhibited in association.
Both anamnesis and the voiding map are diagnosis instruments available to any
doctor, at no cost and with high predictive values for voiding dysfunction diagnosis
.

This being the
case, due to its high positive predictive value, anamnesis in conjunction with
the voiding map as a tool for identifying diurnal symptoms, has been shown to
be an important instrument for voiding dysfunction diagnosis. The lower negative
predictive value draws our attention to the possibility, although less common,
is also possible with MNE.

The study results
reveal a discrepancy between current knowledge about voiding dysfunction and
its application in clinical practice, which makes clear the need to publicize
this information .